Recent experiments showed that divalent antibodies against IgE-receptors on rat mast cells trigger non-cytotoxic histamine release from the cells without participation of cell-bound IgE. Further experiments will be carried out to study whether the participation of the receptors is essential for histamine release. In view of the important role of IgE-receptors on the triggering mechanisms, we shall look for membrane-associated enzymes which may be activated by the bridging of the receptors. Enzyme inhibitors such as 3H-DFP will be employed to identify the enzymes. Since in vitro histamine release from rat mast cells is inconsistent, as compared with the mediator release from mouse mast cells, experiments are designed in collaboration with Dr. H. Ginsburg to use cultured mouse mast cells, which will be established from mouse lymph node cells. The cultured mast cells will be sensitized with either mouse IgE antibody or rat monoclonal IgE for histamine release.